Identification of a Novel Mucin Gene<i>HCG22</i>Associated With Steroid-Induced Ocular Hypertension

Jeong, Shinwu; Patel, N.; Edlund, Christopher K.; Hartiala, Jaana; Hazelett, Dennis J.; Itakura, Tatsuo; Wu, Ping; Avery, Robert L.; Davis, Janet L.; Flynn, Harry W.; Lalwani, Geeta A.; Puliafito, Carmen A.; Wafapoor, H.; Hijikata, Makoto; Keicho, Naoto; Gao, Xiaoyi; Argüeso, Pablo; Allayee, Hooman; Coetzee, Gerhard A.; Pletcher, Mathew T.; Conti, David V.; Schwartz, Stephen G.; Eaton, Alexander M.; Fini, M. Elizabeth

doi:10.1167/iovs.14-14803

Cited by 31 publications

(27 citation statements)

References 97 publications

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“…Several other QTLs with suggestive p-values were also identified in this study (Jeong et al, 2015). The top SNP of a 2 nd peak on chromosome 9 (P = 1.56x10 −7 ) is located in an intragenic region upstream of TLE4 .…”

Section: Pharmacogenomicssupporting

confidence: 74%

“…Data from 64 research subjects survived quality control. Association analysis was performed (as described above), and then combined by a meta-analysis with the 49 subjects of the Florida-1 cohort, for a total of 113 subjects (Jeong et al, 2015). A quantitative trait locus (QTL) was identified at chromosomal position 6p21.33, as shown in Figure 4.…”

Section: Pharmacogenomicsmentioning

confidence: 99%

“…Our bioinformatics analysis revealed that HCG22 is most closely related to peritrophin-A, an ECM protein found in the insect digestive tract (Jeong et al, 2015). The peritrophic matrix functions as a molecular sieve for partially digested protein and carbohydrate, as a barrier to ingested pathogens, as a scaffold for proteases and glycosidases, and as a sink for toxic substances.…”

Section: Pharmacogenomicsmentioning

confidence: 99%

“…We describe the first genome-wide study to identify polymorphisms associated with SIOH (Jeong et al, 2015), and our functional findings on the two novel linked genes, GPR158 (Patel et al, 2013; Patel et al, 2015) and HCG22 (Jeong et al, 2015). There is a great need to identify new drug targets for ocular hypertension, as many patients remain refractory to existing medications and eventually may become blind.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine

Fini

Schwartz

Gao

et al. 2017

Progress in Retinal and Eye Research

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125

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Elevation of intraocular pressure (IOP) due to therapeutic use of glucocorticoids is called steroid-induced ocular hypertension (SIOH); this can lead to steroid-induced glaucoma (SIG). Glucocorticoids initiate signaling cascades ultimately affecting expression of hundreds of genes; this provides the potential for a highly personalized pharmacological response. Studies attempting to define genetic risk factors were undertaken early in the history of glucocorticoid use, however scientific tools available at that time were limited and progress stalled. In contrast, significant advances were made over the ensuing years in defining disease pathophysiology. As the genomics age emerged, it appeared the time was right to renew investigation into genetics. Pharmacogenomics is an unbiased discovery approach, not requiring an underlying hypothesis, and provides a way to pinpoint clinically significant genes and pathways that could not have been discovered any other way. Results of the first genome-wide association study to identify polymorphisms associated with SIOH, and follow-up on two novel genes linked to the disorder, GPR158 and HCG22, is discussed in the second half of the article. However, knowledge of genetic variants determining response to steroids in the eye also has value in its own right as a predictive and diagnostic tool. This article concludes with a discussion of how the Precision Medicine Initiative®, announced by U.S. President Obama in his 2015 State of the Union address, is beginning to touch the practice of ophthalmology. It is argued that SIOH/SIG may provide one of the next opportunities for effective application of precision medicine.

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Section: Pharmacogenomicssupporting

confidence: 74%

Section: Pharmacogenomicsmentioning

confidence: 99%

Section: Pharmacogenomicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine

Fini

Schwartz

Gao

et al. 2017

Progress in Retinal and Eye Research

Self Cite

125

View full text Add to dashboard Cite

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“…In fact, several genes have already been shown to be upregulated in dexamethasone-treated TM cells [10]. The recent identification of two independent intergenic quantitative trait loci (QTL) that could affect expression of the HCG22 mucin gene product found in trabecular meshwork cells may also soon provide further answers [11]. …”

Section: Discussionmentioning

confidence: 99%

Severe Corticosteroid-Induced Ocular Hypertension Requiring Bilateral Trabeculectomies in a Patient with Takayasu’s Arteritis

Gruener

Sharma

Ameen

et al. 2016

Case Reports in Ophthalmological Medicine

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We present a rare case of severe corticosteroid-induced ocular hypertension (OHT) after prolonged systemic corticosteroid use in a young woman with Takayasu's arteritis. As she did not sufficiently respond to ocular antihypertensive therapies, bilateral enhanced trabeculectomies were required to normalize her intraocular pressures. The systemic side effects of corticosteroids are well known, yet steroid-induced OHT and glaucoma remain silent causes of ocular morbidity. This case highlights the importance of IOP-monitoring in visually asymptomatic patients on systemic corticosteroids. It further emphasizes the need to raise awareness of the potential ocular side effects of steroids amongst physicians, in particular those looking after patients with autoimmune and inflammatory diseases.

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Comprehensive bioinformatics analysis identifies lncRNA HCG22 as a migration inhibitor in esophageal squamous cell carcinoma

Xiao

Chang

et al. 2019

J of Cellular Biochemistry

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Esophageal cancer is one of the most lethal malignancies worldwide, and esophageal squamous cell carcinoma (ESCC) is the dominant histological type. However, the long noncoding RNA (lncRNA) alterations in ESCC have not been elucidated to date. In this study, reliable databases from Gene Expression Omnibus (GEO), which analyzed lncRNA expression in ESCC tumor tissues and adjacent normal tissues were searched, and common differentially expressed lncRNAs and genes were analyzed. Next, cis‐ trans analysis was performed to predict the underlying relationships between altered lncRNAs and mRNAs, and the lncRNA‐mRNA regulatory network was established. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of altered lncRNA‐related genes were performed. The promising lncRNA HCG22 was validated by quantitative polymerase chain reaction (qPCR), and clinicopathological data were collected to identify the relationship between lncRNA HCG22 expression level and clinical features. Finally, Transwell assays were performed to explore the biological functions of lncRNA HCG22 in ESCC cells. Two hundred forty‐one lncRNAs and 835 mRNAs were observed to be remarkably altered between ESCC tumor tissues and adjacent normal tissues. The lncRNA‐mRNA regulatory network showed the coexpression association between lncRNA HCG22 and SPINK7 and ADAMTS12. GO and KEGG analyses showed that HCG22 and ADAMTS12 had potential biological functions in the cell migration of ESCC. The downregulation of lncRNA HCG22 in ESCC tumor tissues was validated by qPCR, and the clinicopathological data showed a noticeable correlation between lncRNA HCG22 expression level and the ESCC differentiational degree and clinical TNM stage. Kaplan‐Meier analysis showed that patients with ESCC having low lncRNA HCG22 expression in ESCC tissues had considerably shorter overall survival compared with patients with ESCC having high lncRNA HCG22 expression. Following Transwell assays confirmed the migratory role of lncRNA HCG22 in ESCC cells. In conclusion, lncRNA HCG22 was downregulated in ESCC tissues and can be a migration inhibitor of ESCC cells, and SPINK7 and ADAMTS12 are promising to be the regulatory targets of lncRNA HCG22.

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Identification of a Novel Mucin GeneHCG22Associated With Steroid-Induced Ocular Hypertension

Abstract: Identification of two independent QTLs that could affect expression of the HCG22 mucin gene product via two different mechanisms (transcription or secretion) is highly suggestive of a role in steroid-induced OH.

Cited by 31 publications

References 97 publications

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine

Severe Corticosteroid-Induced Ocular Hypertension Requiring Bilateral Trabeculectomies in a Patient with Takayasu’s Arteritis

Comprehensive bioinformatics analysis identifies lncRNA HCG22 as a migration inhibitor in esophageal squamous cell carcinoma

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